Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Carcinoma progression involves epithelial-mesenchymal transition (EMT), characterized by loss of cell-cell adhesion.
• E-cadherin, a cell adhesion molecule, is crucial for maintaining epithelial phenotype and acts as a metastasis suppressor.
• Akt kinase activation and nuclear factor-kappaB (NF-kappaB) signaling are frequently observed in human carcinomas and implicated in EMT.

Purpose of the Study:

• To investigate the molecular mechanisms linking AKT, NF-kappaB, Snail, and E-cadherin during EMT.
• To elucidate the role of NF-kappaB in Snail-mediated E-cadherin repression.
• To validate the signaling module involving NF-kappaB and Snail in EMT induction.

Main Methods:

• Investigated the dependency of Snail activation and E-cadherin repression on AKT-mediated NF-kappaB activation.
• Assessed the ability of NF-kappaB to induce Snail expression.
• Evaluated the sufficiency of NF-kappaB subunit p65 expression for EMT induction.

Main Results:

• Showed that Snail activation and subsequent E-cadherin repression are dependent on AKT-mediated NF-kappaB activation.
• Demonstrated that NF-kappaB directly induces Snail expression.
• Confirmed that expression of the NF-kappaB subunit p65 is sufficient to induce EMT.

Conclusions:

• The signaling network linking AKT, NF-kappaB, Snail, and E-cadherin plays a critical role in mediating EMT.
• This pathway represents a potential therapeutic target for developing antimetastatic strategies.
• Targeting this network could inhibit tumor progression and metastasis.